Passage
The drug paracetamol, also known as acetaminophen, is used to relieve pain and fever, and is a metabolite of the antipyretic drug phenacetin (Figure 1) . These two drugs have similar medicinal properties, but phenacetin has been shown to be carcinogenic and cause kidney damage. Acetaminophen is a safer alternative to phenacetin when taken in therapeutic doses.
Figure 1 Structure of phenacetinA student synthesizes acetaminophen in a laboratory from phenol according to the reactions shown. The synthesis begins with the nitration of phenol by sodium nitrate (NaNO₃) to produce the mixture of the isomers 2-nitrophenol and 4-nitrophenol (Reaction 1) . These isomers can be easily separated by steam distillation to isolate the desired product, 4-nitrophenol. Reduction of the nitro group with sodium borohydride (NaBH₄) (Reaction 2) is followed by acetylation of the amine with acetic anhydride (Reaction 3) to afford the final product, acetaminophen.
Reaction 1
Reaction 2
Reaction 3
- Normal phase thin layer chromatography (TLC) was used to monitor the formation of acetaminophen. According to the TLC plate shown, which spot has an R_f value of 0.33, and what compound most likely corresponds to this spot?

Question

Passage
The drug paracetamol, also known as acetaminophen, is used to relieve pain and fever, and is a metabolite of the antipyretic drug phenacetin (Figure 1) . These two drugs have similar medicinal properties, but phenacetin has been shown to be carcinogenic and cause kidney damage. Acetaminophen is a safer alternative to phenacetin when taken in therapeutic doses.

Figure 1 Structure of phenacetinA student synthesizes acetaminophen in a laboratory from phenol according to the reactions shown. The synthesis begins with the nitration of phenol by sodium nitrate (NaNO₃) to produce the mixture of the isomers 2-nitrophenol and 4-nitrophenol (Reaction 1) . These isomers can be easily separated by steam distillation to isolate the desired product, 4-nitrophenol. Reduction of the nitro group with sodium borohydride (NaBH₄) (Reaction 2) is followed by acetylation of the amine with acetic anhydride (Reaction 3) to afford the final product, acetaminophen.

Reaction 1

Reaction 2

Reaction 3
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Normal phase thin layer chromatography (TLC) was used to monitor the formation of acetaminophen. According to the TLC plate shown, which spot has an R_f value of 0.33, and what compound most likely corresponds to this spot?

Quizplus · Accepted Answer

11ecba2d_1259_757b_a3bf_81007ea1d13a_MD0008_00 Thin layer chromatography (TLC) is a technique used to separate compounds based on polarity. The mobile phase (organic solvent) travels up the stationary phase, a thin absorbent plate coated with silica (SiO₂), via capillary action. The components of a mixture travel up the plate at different rates based on their polarity. In normal phase TLC, nonpolar compounds have less affinity for the polar stationary phase than polar compounds, and therefore travel farther up the plate. The R_fvalue is expressed by the ratio of the distance traveled by the compound of interest to the distance traveled by the mobile phase. Values can be calculated for A and B as follows: 11ecba2d_1259_9c8c_a3bf_a17e157d075f_MD0008_00 11ecba2d_1259_9c8d_a3bf_4bae95809683_MD0008_00 An R_f value is always less than 1, and a smaller R_f value corresponds to a more polar, less mobile compound. Spot B has an R_f of 0.33 and has traveled a shorter distance up the plate than spot A, making it the more polar compound. To decide whether spot B is 4-aminophenol or acetaminophen, determine which compound is more polar. The only difference between the two compounds is the change from amine in 4-aminophenol to amide in acetaminophen. An amide is a hydrogen bond donor and acceptor via two electronegative atoms (oxygen and nitrogen) whereas an amine (primary and secondary) is a hydrogen bond donor and acceptor via only one electronegative atom (nitrogen). Because an amide has more hydrogen bond acceptors, it is more polar; therefore, spot B must be acetaminophen. (Choices A and C) Spot A has an R_f value of 0.67. (Choices C and D) 4-aminophenol is the less polar compound, and therefore could not be the more polar spot B. Educational objective: Thin layer chromatography is used to separate compounds based on polarity. The R_f value of a compound is a ratio of the distance up the plate a compound travels to the distance the solvent travels. A polar compound will have a smaller R_f value than a nonpolar compound.

Passage the Drug Paracetamol, Also Known as Acetaminophen, Is Used to to Relieve